Nasal delivery of human growth hormone: in vitro and in vivo evaluation of a thiomer/glutathione microparticulate delivery system

• Published in: Journal of controlled release Vol. 100; no. 1; pp. 87 - 95
• Main Authors: Leitner, Verena M., Guggi, Davide, Krauland, Alexander H., Bernkop-Schnürch, Andreas
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.11.2004; Elsevier
• Subjects: Acrylic Resins - administration & dosage; Administration, Intranasal; Animals; Biological and medical sciences; Cysteine - administration & dosage; Drug Delivery Systems; General pharmacology; Glutathione; Glutathione - administration & dosage; hGH; Human Growth Hormone - administration & dosage; Human Growth Hormone - chemistry; Human Growth Hormone - pharmacokinetics; Male; Medical sciences; Microparticulate delivery system; Noninvasive peptide delivery; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Rats; Rats, Wistar; Thiolated polymers; PBS; MWCO; Microparticulate delivery system; Thiolated polymers; hGH; PCP-Cys; PCP; GSH; Noninvasive peptide delivery; Glutathione; Human; Delivery system; Evaluation; Pharmaceutical technology; Peptides; Control release polymer; Somatotropin hormone; Intranasal administration; In vitro; In vivo; Somatropin; Neurohypophyseal hormone; Non invasive method; Microparticle
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/j.jconrel.2004.08.001

It was the aim of this study to develop and evaluate a nasal microparticulate delivery system for human growth hormone (hGH) based on the thiomer polycarbophil-cysteine (PCP-Cys) in combination with the permeation mediator glutathione (GSH). Microparticles were prepared by dissolving PCP-Cys/GSH/hGH (7.5:1:1.5), PCP/hGH (8.5:1.5), and mannitol/hGH (8.5:1.5) in demineralized water, followed by lyophilization and micronization. Particles were evaluated with regard to size distribution and swelling behavior using a laser diffraction particle size analyzer. The release of fluorescence-labelled hGH from microparticles was determined in Franz diffusion chambers. In vivo studies in rats were performed comparing the nasal bioavailability achieved by PCP-Cys/GSH/hGH microparticles with that of unmodified PCP/hGH microparticles and mannitol/hGH powder. PCP-Cys/GSH/hGH and PCP/hGH microparticles showed a comparable size distribution (80% in the range of 4.8–23 μm) and swelled to almost fourfold size in phosphate-buffered saline (PBS). Both formulations exhibited almost identical sustained drug release profiles. The intranasal administration of the PCP-Cys/GSH/hGH microparticulate formulation resulted in a relative bioavailability of 8.11±2.15%, which represents a 3-fold and 3.3-fold improvement compared to that of PCP/hGH microparticles and mannitol/hGH powder, respectively. The study suggests that the PCP-Cys/GSH/hGH nasal microparticulate formulation might represent a promising novel tool for the systemic delivery of hGH.